Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

2 genetic variations predict second cancers after radiation for children with Hodgkin lymphoma

25.07.2011
A genome-wide association study published in the August issue of Nature Medicine has found two tiny genetic variations that can predict which patients with Hodgkin's lymphoma are most likely to develop radiation-induced second cancers years after treatment. Knowing in advance who is at risk could help physicians tailor treatment to reduce the risks for patients who are most susceptible to long-term damage.

Hodgkin's lymphoma is one of the most treatable cancers, with more than 90 percent of patients surviving after a combination of radiation and chemotherapy. But nearly 20 percent of patients treated as children develop a second cancer within 30 years. The younger the patients are when treated and the higher the radiation dose, the greater the risk. This late side effect of treatment is the second leading cause of death for long-term Hodgkin's survivors.

"This finding means we can better identify children who are most susceptible to radiation-induced cancers before treatment begins and modify their care to prevent this serious long-term complication," said Kenan Onel, MD, PhD, associate professor of pediatrics and senior author of the study. "Luckily our options for Hodgkin's are broad enough that we can find ways to control the initial disease without relying on radiation therapy."

"This is also a triumph for genome-wide association studies," he added. "Many previous GWAS studies found multiple genetic differences, with each of them playing only a modest role, with minimal impact on clinical management. In this study, which focused on the interaction between genes and a very specific environmental factor—cancer long after radiation therapy—a small number of genetic differences produced a very big impact."

Onel and colleagues analyzed the genomes of 178 Hodgkin's patients who had been treated between the ages of 8 and 20 with chemotherapy and radiation therapy. Within 30 years after treatment, 96 of them had developed second cancers and 82 had not.

When they scanned each patient's genome, focusing on 665,313 tiny genetic variations known as single nucleotide polymorphisms, they found three variations that appeared far more often in patients with second cancers. When they repeated the study using a different set of patients—62 cases with second cancers and 71 without—two of the three markers were significant.

Those two markers were both from a small region known as 21q on chromosome 6. Both are positioned near a gene known as PRDM1.

The genetic variations closely associated with increased cancer risk, and with each other, appeared to decrease activation of the PRMD1 gene. They had no detectable effect any other genes. Cells with the protective version of both markers expressed PRDM1 after being exposed to radiation. Cells with the variants linked to subsequent cancers did not produce any PRDM1.

Previous studies have found that PRDM1 is involved in a variety of fundamental cellular processes, including proliferation, differentiation and apoptosis—which can all go awry in cancer. The gene's activity is lost in many cancer types.

In Onel's small samples, only three percent of patients with both of the protective variants developed second cancers within 30 years; nearly 33 percent of those with both of the high-risk variations did.

"Taken together," the authors note, "our findings support a novel role for PRDM1 as a radiation-responsive tumor suppressor." PRMD1 may be important for understanding the causes of second cancers in survivors of pediatric Hodgkin's lymphoma as well as in other cancer patients treated with radiation therapy."

This study should also "bring some optimism" back to genome-wide association studies, Onel added. Most previous cancer-related markers found through GWAS have been "of little clinical value for predicting risk, response to therapy or survival." But by incorporating environmental exposure, such as radiation therapy, into genomic investigations, "much of the missing heritability can be revealed," he said. "By folding in the environmental component, we were able to ask a more targeted question. This approach could improve our ability to integrate genomics into routine cancer care."

The National Institutes of Health, the American Cancer Society, American Lebanese Syrian Associated Charities, the Leukemia Lymphoma Society, the Breast Cancer Research Foundation, the Cancer Research Foundation, and the University of Chicago Comprehensive Cancer Center supported this research.

Additional authors include Timothy Best, Andrew Skol, Sarah Jackson, Olufunmilayo Olopade and Stephanie Huang of the University of Chicago; Dalin Li, Thomas Mack, Wendy Cozen and David Conti of University of Southern California; Kenneth Offit and Thomas Kirchhoff of Memorial Sloan Kettering Cancer Center; Yutaka Yasui of the University of Alberta; Smita Bhatia of City of Hope; Louise Strong of the MD Anderson Cancer Center; Susan Domchek and Katherine Nathanson of the University of Pennsylvania; and Leslie Robison of St Jude Children's Research Hospital.

John Easton | EurekAlert!
Further information:
http://www.uchospitals.edu

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>